Open AccessTailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
Author(s) -
Jiang Gan,
Chen Huan,
Huang Jialin,
Song Qingxiang,
Chen Yaoxing,
Gu Xiao,
Jiang Zhenhuan,
Huang Yukun,
Lin Yingying,
Feng Junfeng,
Jiang Jiyao,
Bao Yinghui,
Zheng Gang,
Chen Jun,
Chen Hongzhuan,
Gao Xiaoling
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201903290
Subject(s) - lrp1 , cancer research , pinocytosis , glioma , ldl receptor , internalization , endocytosis , microbiology and biotechnology , downregulation and upregulation , receptor , chemistry , lipoprotein , biology , cholesterol , biochemistry , gene
Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein‐like nanostructure is developed to amplify their internalization into GICs through receptor‐stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor‐stimulated macropinocytosis pathway in GICs, this CXCR4 receptor‐stimulated lipoprotein‐like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA‐34a in the core, this tailored SLNP reduces sex‐determining region Y‐box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs‐bearing mice. Taken together, a tailored lipoprotein‐based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor‐stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.